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The Clinical Trial Participation Experience

By

Byron J. Hoogwerf

, MD, Cleveland Clinic

Last full review/revision Aug 2021| Content last modified Aug 2021
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Patients have different reasons for wanting to participate in clinical trials. Some want access to the newest treatments, which they hope will be more effective than the current standard of care. Participation in a clinical trial is sometimes the only option for people who have serious illnesses and no good treatments are available. Others participate out of a desire to contribute to science. Still others participate to receive the payment made to participants or to gain access to free drugs and medical care provided by the study.

Finding a Clinical Trial

Patients become aware of clinical trials from a variety of sources. Sometimes a physician or other health care practitioner informs the patient about a clinical trial. Even if the physician is not directly involved in a study, the physician may be aware of ongoing studies. This may be more likely if the patient is seeing a physician who is a specialist and, therefore, more aware of ongoing clinical trials. University and academic single-specialty or multi-specialty groups often have clinical trials units. Having a physician suggest a clinical trial is common in many diseases, especially cancers. Many diseases, including cancer, have clinical trial consortiums comprised of centers with expertise in the disease. These consortiums may improve the efficiency or implementation of clinical trials.

Trial recruitment ads run routinely online, in most major newspapers, and on many local radio stations. Some local newspapers and newsletters now publish dedicated weekly sections listing clinical trials. Some trials are advertised through telephone hold messages, bill boards, or social media sites. All solicitations for participation in a clinical trial must be approved in advance by an Institutional Review Board Ethics and Safeguards in Clinical Trials Patients have different reasons for wanting to participate in clinical trials. Some want access to the newest treatments, which they hope will be more effective than the current standard of... read more . Many communities have one or more research centers that consumers can call directly to get information or to get on a mailing list. Almost all clinical trials are listed at ClinicalTrials.gov, a U.S. National Library of Medicine database of privately and publicly funded clinical studies conducted around the world. Some websites help match people to specific trials. For example, the National Institutes of Health (NIH) has an internet-based registry called Research Match that people can use to connect with researchers seeking participants for their trials. CenterWatch is another service that contains thousands of trials that are currently enrolling people.

Helping a Patient Understand Clinical Trials

Clinical trials are complex, and few patients begin the process with adequate understanding of what is involved. Physicians running the trial can provide some guidance throughout the process. A good place to start is to provide patients with a list of questions they should ask to better understand the specific clinical trial they are considering. The study investigator and often a trial coordinator should be actively engaged with the patients, providing information and answering any questions. Following is a list of key questions participants should ask before participating in a clinical trial (1 Reference Patients have different reasons for wanting to participate in clinical trials. Some want access to the newest treatments, which they hope will be more effective than the current standard of... read more ):

  • What is the main purpose of this trial?

  • Does the trial involve a placebo or a treatment that is already on the market?

  • How will the treatment be given to me?

  • How long is the trial going to last?

  • What will I be asked to do as a participant?

  • What has already been learned about the trial treatment and have any trial results been published?

  • Do I have to pay for any part of the trial? Will my insurance cover these costs?

  • Is there any reimbursement for travel costs, parking, or child care?

  • Will I be able to see my own doctor?

  • If the treatment works for me, can I keep using it after the trial has ended?

  • Can anyone find out whether I am participating in a clinical trial?

  • Will I receive any follow-up care after the trial has ended?

  • What will happen to my medical care if I stop participating in the trial?

  • Do the trial doctor and investigator have any financial or special interest in the trial?

  • What are the credentials and research experience of the trial doctor and trial staff?

  • When and how will the results of the trial be provided to me?

  • Will I learn my treatment assignment?

Patients should also ask about what happens if there are any unexpected medical problems.

Reference

  • 1. The Center for Information and Study on Clinical Research Participation: Questions to Ask

Risks and Benefits of Participation in Clinical Trials

Deciding whether to participate in a clinical trial is an important and complicated decision. Physicians can help the patient consider both the risks and benefits.

Risks of participation in clinical trials

Patients should be aware that in a randomized trial they are not guaranteed to receive the new treatment and may instead receive a placebo or other active treatment.

A trial drug may have adverse effects and cause serious reactions, including, on very rare occasions, death. Not all possible adverse effects of the study drug are fully known at the time a patient enters a clinical trial. In fact, a purpose of the trial is to learn what the adverse effects are. Although the researchers try to warn participants of all adverse effects that are known at the time they enroll, unanticipated problems may develop. A similar risk exists for interventions that are procedures, except that the risks for procedures are complications of the procedure, some of which are known but some of which may not yet be known.

The experimental treatment might not work as well as intended, possibly not even as well as standard treatment.

Benefits of participation in clinical trials

There are also some very real potential benefits to clinical trial participation. If a treatment works as expected, participants could have a better outcome than with other treatments normally available to them.

During a clinical trial, participants typically receive excellent care that might otherwise be costly. Because participants are so well monitored, they tend to learn a great deal about their overall health and any underlying medical conditions. Occasionally, the regular monitoring, especially laboratory tests, may detect a separate disease before it becomes clinically evident, allowing for early intervention.

Sometimes there is an opportunity to build camaraderie with other participants, which may be particularly welcome by people who have rare or uncommon diseases.

At a minimum, clinical trial participants can be sure that they are helping to advance medical science and public health.

However, the study team must not guarantee any trial-related benefits. Consent forms for participation should state explicitly that there is no guarantee of benefit.

Ethics and Safeguards in Clinical Trials

In a very small fraction of situations, investigators in charge of clinical trials have acted unethically. One particularly shameful example is known as the Tuskegee experiments. Conducted around Tuskegee, Alabama, from 1932 to 1972, this study enrolled about 400 poor, mostly illiterate, Black sharecroppers who had syphilis. These participants were not told that they had syphilis, and despite the eventual availability of the effective treatment penicillin, the Tuskegee investigators withheld penicillin and information about penicillin purely to continue to study how the disease progressed. Participants were also prevented from accessing syphilis treatment programs that were available to other people in the area. As a result of this serious breach of ethics and trust, several safeguards were put in place. Included in these safeguards are the establishment of Institutional Review Boards and the concept of informed consent.

Institutional Review Boards (IRBs) are specific committees in each medical institution that participate in clinical trials. The purpose of these committees is to ensure that the trial consent form appropriately describes the trial, including its design. If an institution does not have its own IRB, then a central IRB may be used. IRBs must include at least one non-scientific member and at least one member must not be affiliated with that institution. IRBs review all proposed clinical trials involving humans. The purpose of these committees is to ensure that trials are conducted in an ethical manner and to avoid any unreasonable risks associated with the trial design. Only trials that have been approved by the IRB of an institution (or a central IRB) are allowed to proceed in that institution. Each institution's IRB evaluates and approves studies independently from other IRBs. When many different institutions participate in a trial, the U.S. Food and Drug Administration (FDA) permits use of a central IRB that performs the review for that trial. Using a central IRB can eliminate a lot of duplicated effort by separate committees and also ensure a consistent set of protections and requirements at all the study centers. The central IRB for a trial may be the individual IRB at one of the study sites or a private, independent IRB. Central IRBs must still follow all local requirements at each participating site. When trial requirements are governed by law, both independent and central IRBs must ensure that those requirements are included in the trial protocol and the corresponding consent form.

Many interventional studies have an independent data safety monitoring board (DSMB). The DSMB is a committee of experts not affiliated with the trial and who get unblinded data during the trial. The DSMB reviews the data to determine if there is a safety signal (evidence suggesting the possibility of more harm with the intervention than with the control group) of sufficient magnitude to stop the trial (eg, if evidence of efficacy is sufficient) or to determine if the trial may never meet its efficacy goal (called futility) and should be stopped. Evidence of efficacy helps determine whether continuing the trial is worth continued potential safety risks. DSMBs do not make the final decision about a trial but make their recommendations to the sponsor. Sponsors usually accept the recommendation(s) of the DSMB.

Informed consent means that a person is given all the information needed to make an educated and informed decision as to whether to participate in a clinical trial. Information should describe all aspects of the trial, from its purpose to a statement about who pays for medical care to treat any research-related injuries. Informed consent documents tend to be lengthy (in some cases, dozens of pages long), technical, and sometimes use language that may require explanation for the potential trial participant. However, it is essential that participants read the documents carefully. Following are the major elements of informed consent documents (1 References Patients have different reasons for wanting to participate in clinical trials. Some want access to the newest treatments, which they hope will be more effective than the current standard of... read more ):

    • A statement explaining the trial’s purpose, the procedures to be followed, the duration of participation, and any investigational treatments or procedures

    • A description of foreseeable risks and discomforts to participants

    • A description of benefits that the participant can reasonably expect

    • A disclosure of any alternative treatments or procedures that might be advantageous to participants

    • A statement about how participant confidentiality is maintained

    • An explanation of any compensation and whether medical treatments are available if injury occurs

    • A list of contacts to answer trial-related questions and to help with research-related injuries

    • A statement that participation is voluntary and that there is no penalty and no loss of benefits for refusing to participate or discontinuing participation at any time during the trial.

Other elements of informed consent documents that may be included when appropriate include the following:

  • A statement that there may be unforeseeable risks to the participant, embryo, or fetus—if the participant is or may become pregnant

  • A list of circumstances under which the investigator may terminate a participant’s enrollment

  • A description of additional costs to the participant

  • An explanation of the consequences and procedures if a participant decides to withdraw

  • A statement that participants will be informed of significant new findings that might affect their willingness to participate

  • The approximate number of participants enrolled in the trial

If practical, participants should take the informed consent documents home, read them over several times, and discuss them with their personal physician and family members. The physician may be able to help clarify some of the participation risks. Family members and friends particularly need to be involved if they will be providing assistance to the person (such as transportation to the research center). After reviewing the informed consent documents carefully, participants should return them to the investigator and trial coordinator and ask any further questions.

Impaired consent capacity Capacity (Competence) and Incapacity Historically, “incapacity” was considered primarily a clinical finding, and “incompetency” was considered a legal finding. That distinction, at least in terminology, is no longer firmly recognized... read more is an important consideration as mentally disabled persons are a vulnerable category for which IRBs may need to assume increased responsibilities. Impaired consent capacity may be due to a wide range of disorders and conditions, such as dementia, stroke, traumatic brain injury, developmental disorders, serious mental illness, intoxication, and delirium. Enrolling participants with impaired consent capacity raises many considerations and requires additional safeguards, one of which is involvement of a legally authorized representative.

Some trial participant candidates (called vulnerable populations) require greater protection of their rights to ensure that their consent is as truly informed as possible. Vulnerable populations include the following:

  • Children: Children are susceptible to the decisions of their parent or legal guardian.

  • Prisoners: Prisoners may be subject to coercion or pressure.

  • Pregnant women (and the unborn fetus)

With vulnerable patients and with potential candidates with whom investigators have a relationship that could cause pressure to participate (eg, an investigator's own patients, medical trainees, caregivers in the same office or institution), investigators must be careful to ensure the truest possible informed consent.

If a participant is unable to read, the elements of the informed consent documents should be presented orally. An impartial witness should be present, and both the witness and participant need to sign the consent form.

The protection of the safety and rights of clinical trial participants is a task shared by several government agencies as well as the IRBs. However, to a large extent, participants—with the help of their physician, family, and friends—must play an active part in their own protection. The Clinical Trial Participant’s Bill of Rights (2 References Patients have different reasons for wanting to participate in clinical trials. Some want access to the newest treatments, which they hope will be more effective than the current standard of... read more ) can help people understand how to protect their rights during participation. Under the Bill of Rights, any participant who gives consent to participate in a clinical trial or who is asked to give consent on behalf of another has the following rights:

  • To be told the purpose of the clinical trial

  • To be told about all the risks, adverse effects, or discomforts that might be reasonably expected

  • To be told of any benefits that can be reasonably expected

  • To be told what will happen during the trial and whether any procedures, drugs, or devices are different from those that are used as standard medical treatment

  • To be told about available options and how such options may be better or worse than what is being studied in the clinical trial

  • To be allowed to ask any questions about the trial before giving consent and at any time during the course of the trial

  • To be allowed ample time, without pressure, to decide whether to consent to participate

  • To refuse or discontinue participation, for any reason, before and after the trial has started

  • To receive a signed and dated copy of the Informed Consent form

  • To be told of any medical treatments available if complications occur during the trial

Clinical trial participants can always withdraw from a trial for any reason, including if it proves to be uncomfortable or too inconvenient. In addition, a vigilant investigator and trial coordinator will encourage participants to discontinue active treatment if there are changes in their health—such as an allergic or strongly negative reaction to the trial intervention—that make the trial too risky for them to continue. Such participants may be encouraged to participate in appropriate follow-up after leaving the study, whether study-related or not.

Investigators or sponsors may stop a trial if results of interim efficacy analysis indicate lack of efficacy (called "futility") or for safety concerns that affect the benefit/risk assessment of the trial. A blinded trial may also be stopped if participants in one of the groups seem to be having very positive or very negative outcomes compared with participants in the other group. If the trial intervention is very effective, the trial may be stopped. In some such circumstances, placebo participants may receive the intervention and thus the potential benefit. If the trial intervention is ineffective or harmful, the trial may be stopped so that no more of the participants are harmed.

The Health Insurance Portability and Accountability Act (HIPPA) privacy rule also protects clinical research participants by regulating how private health information is shared. In most trials, participants' personal data are kept anonymous by housing each participant's data in a unique and anonymous trial identifier. The U.S. Department of Health and Human Services (HHS) provides information on how HIPAA privacy rules apply to clinical research. In summary, these rules require that a patient's personal health information, such as information in a patient's medical chart or test results, can only be disclosed for research purposes and only if the patient has granted specific written permission. (See HHS.gov for further details of the HIPAA privacy rule.)

References

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Listings of clinical trials are available at:

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